This is an amended application for a renewal of a long standing (31 year) pre- and postdoctoral training program, the theme of which is molecular and cellular mechanisms in cardiovascular disease. The environment is multi-disciplinary consisting of well-funded faculty (total of 21) established in research and training from basic and clinical departments in the College of Medicine (COM) and in several divisions in the Children's Hospital Medical Research Center & Foundation. The administrative structure of the amended grant has been revised. The Internal Advisory Committee (IAC) has been expanded to 5 with a specific rotation plan. Two Co- Pis now assist in the overall functioning of the Program. The External Advisory Committee (EAC) consists of 4 senior outside investigators and convenes semiannually. Collaboration amongst the faculty and trainees is outstanding, with over 187 multi-authored publications in the past 10 years. The faculty provides a vast repertoire of approaches and methods, ranging from the gene to the organism, and the human cardiovascular system, thus providing a wide educational experience for trainees. The transgenic approach is utilized by most faculty, and integrated translational biology is emphasized. The program has been highly successful in training and retention of the highest quality of predoctoral and postdoctoral candidates, and in emphasizing health professionals (Physician/Scientists). The current proposal requests funding for 5 pre- and 5 postdoctoral trainees. Predocs are selected by the IAC from a wide pool arising from departments, the successful Flex program, a funded PSTP and a Short-Term Medical Student & ASPET -supported programs. Postdoctoral fellows, are nominated by faculty, and must be approved by the IAC. A specific plan and benchmarks for successful progress are in place. The mentoring is detailed, and includes mentoring of junior faculty. Evaluation (annually) of the mentoring of trainees utilizes the NHLBI Mentoring Evaluation Form sent to the IAC. Recruitment of minorities has been very successful. A new URL, http://heartrresearch.minority. opp. googlepages.com, has been developed. In the post genomic era our challenge as cardiovascular biomedical scientists is to meaningfully characterize how genes function and underlie critical physiologic processes and disease.